Fig. 18.13 ), right ventricular output exceeds left ventricular output. Hence, venous return to the left ventricle (a function of right ventricular output) exceeds left ventricular output, and left ventricular diastolic volume and pressure rise. According to the Frank-Starling mechanism, left ventricular output therefore increases (from point B toward point C in
Fig. 18.13 ). Only when the output of both ventricles is identical (points A and C) is equilibrium reached. Under such conditions, however, left atrial pressure (point C) exceeds right atrial pressure (point A). This is precisely the relationship that ordinarily prevails.
Thefactthatleftatrialpressureexceedsrightatrialpressureaccountsfortheobservationthatinindividualswithcongenitalatrialseptaldefectsinwhichthetwoatriacommunicatewitheachotherviaapatentforamenovale,thedirectionofshuntflowisusuallyfromlefttotherightsideoftheheart.
•Fig. 18.13 Relationships Between the Output of the Right and Left Ventricles and Mean Pressure in the Right and Left Atria, Respectively. Atanygivenlevelofcardiacoutput,meanleftatrialpressure(e.g.,pointC)exceedsmeanrightatrialpressure(pointA).Atrial pressure Right Left A C B Cardiac output
Force0.632020 •Fig. 18.14 Changesindevelopmentofforce(y-axis)inanisolatedpapillarymuscleastheintervalbetweencontractionsisvariedfrom20secondsto0.63secondandthenbackto20seconds.(RedrawnfromKoch-WeserJ,BlinksJR.Pharmacol Rev. 1963;15:601.)
Myocardial performance is also regulated by changes in the frequency at which the myocardial fibers contract. The effects of changes in contraction frequency on the force developed in an isometrically contracting papillary muscle are shown in
Fig. 18.14 . Initially, the cardiac muscle is stimulated to contract once every 20 seconds. When the muscle is suddenly made to contract once every 0.63 seconds, the force developed increases progressively over the next several beats. At the new steady state, the force developed is more than five times greater than the force at the larger contraction interval. A return to the larger interval (20 seconds) has the opposite influence on the development of force.
The rise in the force developed when the contraction interval is decreased is caused by a gradual increase in intracellular [Ca++]. Two mechanisms contribute to the rise in intracellular [Ca++]: an increase in the number of depolarizations per minute and an increase in the inward Ca++ current per depolarization.
In the first mechanism, Ca++ enters the myocardial cell during each action potential plateau (see ). As the interval between beats is diminished, the number of plateaus per minute increases. Although the duration of •Fig. 18.15 Calcium Currents Induced in a Myocyte During the First (Labeled 1) and Seventh (Labeled 7) Depolarizations in a Consecutive Sequence of Depolarizations. Thearrows indicatethehalf-timesofinactivationofthecalciumcurrent,asobtainedfromkineticanalysis.Bytheseventhdepolarization,themaximalinwardrectifyingcalciumcurrenthadincreasedbymorethan50%,andthehalf-timeofinactivationhadincreasedby20msec.(ModifiedfromLeeKS.Proc Natl Acad Sci U S A. 1987;84:3941.) each action potential (and of each plateau) decreases as the interval between beats is reduced, the overriding effect of the increased number of plateaus per minute on the influx of Ca++ prevails, and intracellular [Ca++] increases.
In the second mechanism, as the interval between beats is suddenly diminished, the inward rectifying calcium current (iCa) progressively increases with each successive beat until a new steady state is attained at the new basic cycle length. In an isolated ventricular myocyte, influx of Ca++ into the myocyte increases on successive depolarizations (